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Dr. Elmer Verner McCollum (1879 - 1967) and Vitamin D

June 8, 2020

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History of Medicine
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Dr. Elmer Verner McCollum
Photo credit: by Unknown author - UW-Madison Archives S04394, Public Domain; Wikipedia Commons

American researchers Elmer McCollum and Marguerite Davis in 1914 discovered a substance in cod liver oil which later was called "vitamin A". British doctor Edward Mellanby noticed dogs that were fed cod liver oil did not develop rickets and concluded vitamin A, or a closely associated factor, could prevent the disease. In 1922, Elmer McCollum tested modified cod liver oil in which the vitamin A had been destroyed. The modified oil cured the sick dogs, so McCollum concluded the factor in cod liver oil which cured rickets was distinct from vitamin A. He called it vitamin D because it was the fourth vitamin to be named. It was not initially realized that, unlike other vitamins, vitamin D can be synthesized by humans through exposure to UV light.

In 1925, it was established that when 7-dehydrocholesterol is irradiated with light, a form of a fat-soluble vitamin is produced (now known as D3). Alfred Fabian Hess stated: “Light equals vitamin D.“ Adolf Windaus, at the University of G?ttingen in Germany, received the Nobel Prize in Chemistry in 1928 for his work on the constitution of sterols and their connection with vitamins. In 1929, a group at NIMR in Hampstead, London, were working on the structure of vitamin D, which was still unknown, as well as the structure of steroids. A meeting took place with J.B.S. Haldane, J.D. Bernal, and Dorothy Crowfoot to discuss possible structures, which contributed to bringing a team together. X-ray crystallography demonstrated the sterol molecules were flat, not as proposed by the German team led by Windaus. In 1932, Otto Rosenheim and Harold King published a paper putting forward structures for sterols and bile acids which found immediate acceptance. The informal academic collaboration between the team members Robert Benedict Bourdillon, Otto Rosenheim, Harold King, and Kenneth Callow was very productive and led to the isolation and characterization of vitamin D. At this time, the policy of the Medical Research Council was not to patent discoveries, believing the results of medical research should be open to everybody. In the 1930s, Windaus clarified further the chemical structure of vitamin D.

In 1923, American biochemist Harry Steenbock, a student of Elmer McCollum, at the University of Wisconsin demonstrated that irradiation by ultraviolet light increased the vitamin D content of foods and other organic materials. After irradiating rodent food, Steenbock discovered the rodents were cured of rickets. A vitamin D deficiency is a known cause of rickets. Using $300 of his own money, Steenbock patented his invention. His irradiation technique was used for foodstuffs, most memorably for milk. By the expiration of his patent in 1945, rickets had been all but eliminated in the US.

Elmer Verner McCollum (March 3, 1879 - November 15, 1967) was an American biochemist known for his work on the influence of diet on health. McCollum is also remembered for starting the first rat colony in the United States to be used for nutrition research. Living at a time when vitamins were unknown, McCollum asked and tried to answer the questions, “How many dietary essentials are there, and what are they?“ He and Marguerite Davis discovered the first vitamin, named A, in 1913. McCollum also helped to discover vitamin B and vitamin D and worked out the effect of trace elements in the diet. As a worker in Wisconsin and later at Johns Hopkins, McCollum acted partly at the request of the dairy industry. When he said that milk was “the greatest of all protective foods“, milk consumption in the United States doubled between 1918 and 1928. McCollum also promoted leafy greens, which had no industry advocates.

McCollum's ancestors immigrated to the United States from Scotland in 1763. McCollum was born in 1879 to Cornelius Armstrong McCollum and Martha Catherine Kidwell McCollum on a farm 3 miles from Redfield, Kansas, usually reported to have been Fort Scott, Kansas, which was 11 miles away. McCollum spent his first seventeen years on this farm and attended a one-room school. At some point he had surgery for a detached retina, which the doctors were unable to "glue back again".

While a junior in college, McCollum was elected to Sigma Xi, a non-profit honor society for those interested in science and engineering. As his mother had hoped, McCollum graduated from the University of Kansas in 1903. While there, he abandoned the dream of becoming a doctor, and during his sophomore year, he consumed organic chemistry, earning a bachelor's degree in three years, followed by his master's in 1904. He secured a scholarship to Yale University in 1904, and wrote his thesis on pyrimidines. McCollum got his Ph.D. from Yale in two years, and remained for another year as a postdoctoral researcher working with Thomas Osborne and Lafayette Mendel on plant protein and diet.

The University of Wisconsin Dairy Barn Site of the Single-Grain Experiment.

In Wisconsin, McCollum was assigned to analyze cow feed and the animal's milk, blood, feces, and urine for the famous single-grain experiment, directed by department chief Stephen Babcock and his successor Edwin B. Hart. The experiment ran for four years until 1911. Babcock had studied for his Ph.D. at the University of Gottingen in Germany prior to working at the New York State Agricultural Experiment Station and then joining the staff in Wisconsin. During this era, German chemists were trying to create the perfect foods for farm animals. Due to discoveries by Justus von Liebig and others, they thought that any feed that contains a set amount of protein, carbohydrates, fats, salts, and water was equivalent to any other. Babcock did not believe them, and joked with his German colleagues that cows could survive on coal and ground-up leather according to their calculations.

Sixteen calves were purchased on the market. One was part Jersey and one was part Guernsey. Three out of four groups of calves were given feed prepared from a single grain and raised until they had had two pregnancies. One group received wheat, the second received oats, while the third ate only corn. A fourth group received a combination of all three grains. After the first year, only the corn group was thriving, and the others and their young were weak or dying. The wheat group was the worst off, and the oats and mixed groups were in between. When the weak cows were fed corn, they recovered and bore healthy calves. Hart and his team published their findings in 1911 in Physiological Effect on Growth and Reproduction of Rations Balanced from Restricted Sources. The researchers and Babcock, the leader, could see the results but, they write, “At present we have no solution for the observations made.“ McCollum summarized, “something fundamental remained to be discovered.“

Rat Colony

Searching for a breakthrough in human and animal nutrition, McCollum purchased all thirty-seven volumes of Richard Maly's Jahresbericht Uber Die Fortschritte Der Tier-Chemie. He read of about 13 experiments done between 1873 and 1906 on small animals, often mice, fed restricted diets. In all cases, the animals failed to thrive and died in a few weeks. McCollum determined that he must find out what was lacking in their purified diets, and that he needed to experiment on animals with a short life span, finally deciding on rats. Rats are omnivorous, and cheaply fed, matured quickly, and “had little sentimental and no positive economic value“. The dean of the college of agriculture would not support experiments with what he feared was vermin, but Babcock, who was retired, understood the rats' importance and told McCollum to proceed. Using skills he developed with his brother when they were children, McCollum captured some rats from a horse barn, but they were too vicious and wild. He replaced them with twelve young albino rats with some domestication that he bought for $6 from a Chicago pet store. His rat colony, started in January 1908, was the first in America used for nutrition research.

Discovery of Vitamin A

McCollum was still responsible for the care of the heifers until 1911, and the care and feeding of his rats fell to a new volunteer, Marguerite Davis, a home economics-turned-biochemistry student who looked out for them daily. Davis helped McCollum develop "the biological method for the analysis of food", and she co-authored a number of papers. Among them was "The Necessity Of Certain Lipins In The Diet During Growth" in 1913. They fed rats pure casein, carbohydrates (lactose, dextrine, and/or starch), with a little agar-agar and a mixture of six or seven salts. They substituted lard or olive oil for some of the carbohydrates for a group of rats. For 70 to 120 days, their rats grew, and then they stopped growing. They still appeared to be healthy, except the females did not have enough milk to nourish their young. They successfully restored about thirty rats to normality, after these rats had reached the stage of growth suspension, by adding a small amount of extracts of egg or butter. Their paper included charts for five rats, illustrating their weights over time compared to a normal growth curve, meant to show McCollum and Davis's "almost invariable success in inducing a resumption of growth after complete suspension for a time". One chart showed their results with a fat-free diet. They became convinced that without a substance in the egg or butter extract, rats could not grow, even though they appeared to be healthy. They concluded that rats stop growing until they are fed certain "ether extracts of egg or of butter", and that "there are certain accessory articles in certain food-stuffs which are essential for normal growth for extended periods". They also found this food factor in extracts of alfalfa leaves and in organ meats. This substance that McCollum called "factor A," was later called vitamin A. McCollum and Davis, who ultimately received credit for the discovery, submitted their paper for publication three weeks before Osborne and Mendel. Both papers appeared in the same issue of the Journal of Biological Chemistry in 1913. This turned out to be a very close call given that learning about vitamin A took scientists about 130 years, beginning with Fran?ois Magendie in 1816 through its synthesis in 1947.

Discovery of Vitamin B

Looking at beriberi and the problem of polished rice, Christiaan Eijkman and Gerrit Grijns were trying to find the cause of polyneuritis (influenced by Louis Pasteur. Eijkman thought bacteria caused beriberi, but McCollum's approach differed in that he was seeking the reason for failure in growth. McCollum and Davis's experiments with rat diets led to the discovery that Eijkman's and Grijns' anti-neuritic substance was the same as their water-soluble B[3] (B vitamins) in 1915. The finding is number 8 in their list of conclusions, "The water-soluble accessory is not the same one as is furnished by butter fat. 20 percent addition of butter fat does not induce any growth unless the other accessory is supplied." He later found that B is actually combined from many different compounds. In 1916 McCollum and Cornelia Kennedy named the factors with alphabetical letters.

Move to Johns Hopkins

In 1917 the Rockefeller Foundation established a new Department of Chemical Hygiene at Johns Hopkins University, and the unconventional founder's first two appointments were to non-medical scientists working for agricultural experiment stations. McCollum was offered the chairmanship and a professorship, although he almost did not get the job. William H. Howell, assistant director of the new school, said, "We had just one misgiving about appointing you to a professorship, McCollum. You look so frail." Indeed, McCollum was six feet tall but weighed only 127 pounds.

McCollum was elected a member of the National Academy of Sciences in 1920. He became emeritus professor in 1945. During his over twenty-five years at Johns Hopkins, McCollum published about 150 papers. His work was on fluorine and the prevention of tooth decay, vitamins D and E, and the effect of a slew of trace minerals in nutrition, including aluminum, calcium, cobalt, phosphorus, potassium, manganese, sodium, strontium, and zinc.

McCollum worked with Herbert Hoover's U.S. Food Administration to help those who were starving in Europe following World War I. Hoover sent him on a lecture tour of all the major cities in the western U.S., where McCollum explained that the American diet was of poor quality, and that it would be better to eat organ meats (rather than muscle meats), fewer potatoes, and less sugar.

Discovery of Vitamin D

In conversation with John Howland, a Johns Hopkins pediatrician, and later with Howland's staff doctors Edwards A. Park and Paul G. Shipley, they found that rickets could be induced through diet. McCollum's research during the early 1920s found that rats could develop rickets when fed a plain cereal diet. His group tested more than 300 diets on rats, finally finding that cod-liver oil could prevent rickets. Building on the work of Edward Mellanby, who had been inspired by the discovery of vitamin A by McCollum and Davis, McCollum fed animals with induced rickets cod liver oil that was heated and aerated so its vitamin A was destroyed. The oil could no longer cure night blindness but did cure rickets. After his rats recovered, he named the substance for the next free letter of the alphabet, vitamin D. Then they became convinced that sunshine and cod-liver oil both protected against rickets and tested this by carrying rats outside to the sunshine. Soon after, a generation of children grew up on cod-liver oil, and rickets was virtually wiped out.

Dairy Industry Ties

Like his predecessors at Wisconsin, McCollum was always mindful of the dairy industry. At his suggestion, the National Dairy Council was formed in 1915. While at Johns Hopkins, he was the leader of the National Dairy Products Corporation research laboratory and served as a consultant there, for one hour per day and one evening per week. (National Dairy became Kraft Foods Inc and is known today as Mondelez International and Kraft Heinz). An ad for Formulac infant formula appeared in the Journal of the Indiana State Medical Association in 1947. Developed by McCollum and marketed by Kraft Foods, Inc., the formula of concentrated milk contained all known vitamins necessary for "proper infant nutrition". McCollum wanted milk to be fortified with vitamin D. Today, the National Dairy Council's website welcomes researchers, saying that it was McCollum "who first made the scientific connection between dairy foods and good health". In 1942 he wrote an article, "What Is the Right Diet?" for The New York Times Magazine. He says there are about forty essential ingredients in the human diet: at least ten of the 22 amino acids, four vitamins (A, D, E, K) that are fat-soluble, nine water-soluble vitamins (C, and various B vitamins), one fatty acid, dextrose, at least thirteen minerals, water, and oxygen.

Public Health Advocacy

He gave the Harvey Lectures in 1917, with the title, "The Supplementary Relations among Our Common Foodstuffs". McCollum's textbook The Newer Knowledge of Nutrition (1918) influenced many dietitians and went through multiple editions coauthored by Nina Simmonds and Elsa Orent-Keiles. In this book he introduced his idea of "protective foods". He wrote that the American diet was of poor quality because it had too much "white flour or cornmeal, muscle meats, potatoes, and sugar". He encouraged a daily quart of milk and lots of green, leafy vegetables. Not surprisingly, McCollum also promoted lacto-vegetarianism. Under the title "Our Daily Diet", between 1922 and 1946 McCollum wrote about 160 columns for McCall's magazine. He tackled topics like, "Are there such things as nerve foods?" and "Green vegetables are unbottled medicines." McCollum was the nutrition editor of the magazines McCall's and Parents. He was on the editorial boards of the Journal of Nutrition, the Journal of Biological Chemistry, and Nutrition Reviews.

Long interested in the effect of diet on the teeth, McCollum was awarded medals by the Connecticut and Ohio dental societies and was a fellow of the New York society as well as an honorary member of the American Academy of Dental Medicine. His paper "The Effect Of Additions Of Fluorine to the Diet Of The Rat On the Quality Of the Teeth" (1925) described how excessive florine would negatively affect dental health in rats. Nonetheless, McCollum would later become a supporter of water fluoridation from the beginning of recorded evidence for the intervention. In 1938 the U.S. Public Health Service reported that adding fluoride to drinking water resulted in fewer dental caries. McCollum was moderator of "The Cause and Prevention of Dental Caries", sponsored by the Good Teeth Council for Children, Inc., that same month. His 1941 article "Diet in Relation to Dental Caries" claimed that vigorous chewing exercises teeth to retain optimum health, that chewing foods has a detergent effect, and that "protective action of excessive fat in the diet may possibly be due to greasing the tooth surface and the cavity surface".

As a new member of the Food and Nutrition Board, McCollum was part of the decision in 1941 to enrich bread and flour with thiamine, niacin, and iron. McCollum was critical of the decision; while he agreed that white bread has nutritional deficiencies, he felt that this action did not compensate for all of the nutrients that are stripped away by milling. In the ensuing controversy, McCollum's status was changed from "board member" to "panel member" and he was no longer invited to board meetings. For years, he continued to think his own plan of adding "nonfat milk solids, brewer's yeast, and wheat and corn germs" was superior to the plan as enacted.

McCollum's Health

At seven months of age, McCollum fell ill with what we know today as scurvy when his mother became pregnant. She weaned him on mashed potatoes and boiled milk. McCollum was slowly dying, and had painful sores, bleeding gums, and swollen joints. One day while his mother was peeling apples, McCollum started to suck on the peels. When on the following day he felt a little better, she fed him more apple skins. When spring came, she gave him other fruits and vegetables. McCollum completely recovered from scurvy, but his teeth caused him trouble for the rest of his life. Finally, in 1926 he had all his teeth removed and got dentures. His health improved.

McCollum suffered from diverticulitis, and was often in pain. He had a number of operations, and finally his descending colon was removed. Again his health improved. McCollum was blind in his left eye because of a detached retina that doctors were unable to repair.

Retirement and Death

After his 1944 retirement as professor emeritus, he spent ten years writing The History of Nutrition; he also wrote his autobiography, From Kansas Farm Boy to Scientist.

In 1961 he was elected a foreign member of the Royal Society. And in 1965 the University of Kansas named a ten-story dormitory, McCollum Hall, after McCollum and his brother Burton. The building housed about nine hundred students for fifty years until it was demolished in 2015. Each of them sat for a portrait painted by Kansas artist Daniel MacMorris. The portraits hung side by side in the foyer. After the demolition, McCollum's portrait was moved to the School of Pharmacy, and Burton's went to the Kansas Geological Survey. One issue became especially important to him, and he wrote dozens of his friends asking what could be done about it. He thought the country was losing its potassium and phosphorus, and he wanted to find a way to recycle them instead of throwing them in our sewage.

In 1965 he and his wife traveled so he could speak at the fiftieth anniversary of the appointment of Agnes Fay Morgan to the faculty of the University of California, Berkeley. The following year, he was unable to attend the 100th anniversary of the University of Kansas in 1966 because of physical disability.

McCollum died on November 15, 1967, at the age of 88. Shortly before his death, he remarked: "I have had an exceptionally pleasant life and am thankful."

Source: Wikipedia

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